Drug target discovery today is to a large extent based on the design of individual effector molecules on the basis of known target structures. Modern drug design is also based on single receptor-ligand interactions. In nature this is often not the case, as is exemplified by many viruses, which interact with more than one receptor. HIT has been shown to bind to both CD4 and chemokine receptors such as CCR5, and adenoviruses have been shown to bind both to integrins and to the CAR-protein. In addition to these, additional receptors have recently been identified. It seems likely that this concept is general and that efficient uptake of particles, such as viruses, is caused by the combined interaction with two or possibly more receptors. It is known from the study of adenoviruses that one of the constraints in viral particle uptake is the positioning of the ligands for integrins and for CAR. Thus the shafts or antennae of the adenoviral particle need to be of a certain length in order for internalisation. For most two-receptor systems, very little is however known about the optimal distances between the ligands, their orientation and exact mechanisms of interaction.